Serum levels of TNF-α, IFN-γ, NGF, and CNTF in children with autism spectrum disorder.
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The etiopathogenesis of autism spectrum disorder (ASD) remains incompletely understood but involves dysregulation across multiple biological systems, including pro-inflammatory cytokine networks and neurotrophic signaling pathways. This study measured serum concentrations of pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ), alongside neurotrophic factors nerve growth factor (NGF) and ciliary neurotrophic factor (CNTF), in children diagnosed with ASD compared to neurotypical controls. A secondary aim was to examine associations with ASD symptom severity. Participants included 60 children with ASD (86.7% male, mean age 9.4 ± 0.6 years) and 29 controls (79.3% male, mean age 8.0 ± 0.4 years), ASD severity was classified per DSM-5-TR criteria (Level I: n = 19; Levels II-III: n = 41). Serum analyses revealed elevated TNF-α (p = 0.048), NGF (p = 0.045), and CNTF (p = 0.032) in the ASD group compared to controls, with IFN-γ showing a non-significant increase (p = 0.279). However, biomarker levels showed no significant differences across ASD severity subgroups (Level I vs. Levels II-III vs. controls; all adjusted p > 0.14 following multiple testing correction). Spearman correlations demonstrated positive associations between all four biomarkers and ASD symptom severity scores (all p = 0.0001). In conclusion, the findings demonstrate altered serum profiles of selected inflammatory and neurotrophic markers in children with ASD and highlight strong interrelationships among these biomarkers. Although no significant associations with symptom severity were identified, the results support the involvement of dysregulated neuroimmune and neurotrophic signaling in ASD pathophysiology and warrant further investigation in larger, longitudinal studies.